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Lineage relationship of prostate cancer cell types based on gene expression.

Pascal LE, Vêncio RZ, Vessella RL, Ware CB, Vêncio EF, Denyer G, Liu AY - BMC Med Genomics (2011)

Bottom Line: The non-luminal-like types showed expression more similar to that of stem/progenitor cells than the luminal-like types.However, none showed expression of stem cell genes known to maintain stemness.Non-luminal-like types are all representatives of aggressive disease, and this could be attributed to the similarity in overall gene expression to stem and progenitor cell types.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Urology University of Washington, Seattle, WA 98195, USA.

ABSTRACT

Background: Prostate tumor heterogeneity is a major factor in disease management. Heterogeneity could be due to multiple cancer cell types with distinct gene expression. Of clinical importance is the so-called cancer stem cell type. Cell type-specific transcriptomes are used to examine lineage relationship among cancer cell types and their expression similarity to normal cell types including stem/progenitor cells.

Methods: Transcriptomes were determined by Affymetrix DNA array analysis for the following cell types. Putative prostate progenitor cell populations were characterized and isolated by expression of the membrane transporter ABCG2. Stem cells were represented by embryonic stem and embryonal carcinoma cells. The cancer cell types were Gleason pattern 3 (glandular histomorphology) and pattern 4 (aglandular) sorted from primary tumors, cultured prostate cancer cell lines originally established from metastatic lesions, xenografts LuCaP 35 (adenocarcinoma phenotype) and LuCaP 49 (neuroendocrine/small cell carcinoma) grown in mice. No detectable gene expression differences were detected among serial passages of the LuCaP xenografts.

Results: Based on transcriptomes, the different cancer cell types could be clustered into a luminal-like grouping and a non-luminal-like (also not basal-like) grouping. The non-luminal-like types showed expression more similar to that of stem/progenitor cells than the luminal-like types. However, none showed expression of stem cell genes known to maintain stemness.

Conclusions: Non-luminal-like types are all representatives of aggressive disease, and this could be attributed to the similarity in overall gene expression to stem and progenitor cell types.

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Differential gene expression among cancer cell types. A: Shown is the dataset query display of selected genes among the cell types listed. B: Shown is the query display for seven selected genes among the non-luminal-like cancer cell types.
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Figure 5: Differential gene expression among cancer cell types. A: Shown is the dataset query display of selected genes among the cell types listed. B: Shown is the query display for seven selected genes among the non-luminal-like cancer cell types.

Mentions: Like 5D3 and SP cells, the different non-luminal-like prostate cancer cell types showed little expression of LIN28, POU5F1, NANOG, SOX2 (Figure 5A). This was not unexpected for the luminal-like types. The cancer cells (except LuCaP49) could be distinguished by their expression of any one of the cancer genes AMACR, PCA3, AGR2; their expression levels were variable. LuCaP 49 had signals for KIT (CD117) and SOX2 in addition to PROM1. Both 5D3 and SP also showed expression of KIT. A single cell type with this marker was reported to be capable of generating a prostate [33]. Figure 5B shows the expression pattern of several other genes in these cancer cell types. Except for G4, AR expression was minimal in the other non-luminal-like types and the progenitor cells. CD44, CD49f, CD271, CD138 are basal cell markers, and some could be detected in the cancer cells. Note the lower expression of CD44, by comparison, in the ES and EC cells. LuCaP 49 showed markers of neuroendocrine differentiation CD56 and CD57, and was unique in that regard.


Lineage relationship of prostate cancer cell types based on gene expression.

Pascal LE, Vêncio RZ, Vessella RL, Ware CB, Vêncio EF, Denyer G, Liu AY - BMC Med Genomics (2011)

Differential gene expression among cancer cell types. A: Shown is the dataset query display of selected genes among the cell types listed. B: Shown is the query display for seven selected genes among the non-luminal-like cancer cell types.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3113924&req=5

Figure 5: Differential gene expression among cancer cell types. A: Shown is the dataset query display of selected genes among the cell types listed. B: Shown is the query display for seven selected genes among the non-luminal-like cancer cell types.
Mentions: Like 5D3 and SP cells, the different non-luminal-like prostate cancer cell types showed little expression of LIN28, POU5F1, NANOG, SOX2 (Figure 5A). This was not unexpected for the luminal-like types. The cancer cells (except LuCaP49) could be distinguished by their expression of any one of the cancer genes AMACR, PCA3, AGR2; their expression levels were variable. LuCaP 49 had signals for KIT (CD117) and SOX2 in addition to PROM1. Both 5D3 and SP also showed expression of KIT. A single cell type with this marker was reported to be capable of generating a prostate [33]. Figure 5B shows the expression pattern of several other genes in these cancer cell types. Except for G4, AR expression was minimal in the other non-luminal-like types and the progenitor cells. CD44, CD49f, CD271, CD138 are basal cell markers, and some could be detected in the cancer cells. Note the lower expression of CD44, by comparison, in the ES and EC cells. LuCaP 49 showed markers of neuroendocrine differentiation CD56 and CD57, and was unique in that regard.

Bottom Line: The non-luminal-like types showed expression more similar to that of stem/progenitor cells than the luminal-like types.However, none showed expression of stem cell genes known to maintain stemness.Non-luminal-like types are all representatives of aggressive disease, and this could be attributed to the similarity in overall gene expression to stem and progenitor cell types.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Urology University of Washington, Seattle, WA 98195, USA.

ABSTRACT

Background: Prostate tumor heterogeneity is a major factor in disease management. Heterogeneity could be due to multiple cancer cell types with distinct gene expression. Of clinical importance is the so-called cancer stem cell type. Cell type-specific transcriptomes are used to examine lineage relationship among cancer cell types and their expression similarity to normal cell types including stem/progenitor cells.

Methods: Transcriptomes were determined by Affymetrix DNA array analysis for the following cell types. Putative prostate progenitor cell populations were characterized and isolated by expression of the membrane transporter ABCG2. Stem cells were represented by embryonic stem and embryonal carcinoma cells. The cancer cell types were Gleason pattern 3 (glandular histomorphology) and pattern 4 (aglandular) sorted from primary tumors, cultured prostate cancer cell lines originally established from metastatic lesions, xenografts LuCaP 35 (adenocarcinoma phenotype) and LuCaP 49 (neuroendocrine/small cell carcinoma) grown in mice. No detectable gene expression differences were detected among serial passages of the LuCaP xenografts.

Results: Based on transcriptomes, the different cancer cell types could be clustered into a luminal-like grouping and a non-luminal-like (also not basal-like) grouping. The non-luminal-like types showed expression more similar to that of stem/progenitor cells than the luminal-like types. However, none showed expression of stem cell genes known to maintain stemness.

Conclusions: Non-luminal-like types are all representatives of aggressive disease, and this could be attributed to the similarity in overall gene expression to stem and progenitor cell types.

Show MeSH
Related in: MedlinePlus